JAX
Mouse Strain Datasheet - 004694
B6;D2-Tg(TcrLCMV)327Sdz/JDvsJ
Also Known As: B6;D2-TCR LCMV
Mice carry a transgenic TCR allowing the examination of T-cell tolerance to two independent antigens with the same transgenic mouse line.
Donating Investigator
Dr. David Serreze, The Jackson Laboratory
Genetic overview
| Genetic Background | Generation |
|---|---|
|
N2F8p+F5
|
Tg(TcrLCMV)327Sdz
| Allele Type |
|---|
| Transgenic (Inserted expressed sequence) |
Detailed Description
These mice carry a T-cell receptor (Tcra-V2, Tcra-J TA31 / Tcrb-V8.1, Tcrb-D, Tcrb-J 2.4) specific for LCMV (lymphocytic choriomeningitis virus), H2-Db . They offer the unique possibility to examine T-cell tolerance to two independent antigens with the same transgenic mouse line. First, T-cell tolerance to LCMV has been studied in transgenic mice carrying the non-cytopathic LCM virus after neonatal infection. Second, the transgenic TCR use the beta-chain variable gene segment Tcrb-V8.1 that reacts preferentially with Mlsa (mixed lymphocyte stimulatory) antigen. Ten to twenty copies of the Tcr transgene are reportedly integrated on the same chromosome. The animals are on a mixed C57BL/6 and DBA/2 background but the MHC haplotype has been checked and found to be H2b.
Development
Zinkernagel et al, established a set of LCMV-specific cytotoxic T-cell clones from lethally irradiated B10.BR/SgSn(H-2K reconstituted with T-cell depleted C57BL/10Sn (H-2bbone marrow cells. The rearranged TCR alpha (Tcra-V2 and Tcra-J TA31) and beta (Tcrb-V8.1, TcrB-D, TcrB-J2.4) chain gene sequences from clone P14 were incorporated into transgene contructs regulated by the H-2Kbpromoter and co-injected into B6D2F2 fertilized embryos. 10-20 copies of both the alpha and beta transgenes co-integrated on the same chromosome in male founder number 327. Founder 327 was backcrossed to C57BL/6J for one generation prior to being intercrossed to make this a homozygous strain. This strain is maintained by homozygous sibling matings.
Expression Data
| Expressed Gene | Tcra, T cell receptor alpha chain, mouse, laboratory |
|---|---|
| Expressed Gene | Tcrb, T cell receptor beta chain, mouse, laboratory |
| Site of Expression |
Control Suggestions
- There are no appropriate physiological controls for this mutant strain. However, if you must have a control you may use any of the following strains: B6D2F1/J (Stock No. 100006), C57BL/6J (Stock No. 000664), and DBA/2J (Stock No. 000671). These strains also serve as DNA controls.
Approximate Controls
Additional Information
Selected References
- Pircher H; Burki K; Lang R; Hengartner H; Zinkernagel RM. 1989. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342(6249):559-61. PubMed: 2573841MGI: J:77696
Tg(TcrLCMV)327Sdz
Allele Symbol: Tg(TcrLCMV)327Sdz
| Allele Name | transgene insertion 327, Birgit Ledermann |
|---|---|
| Allele Type | Transgenic (Inserted expressed sequence) |
| Allele Synonym(s) | P14; P14 TCR; P14 TCR-alphabeta (Valpha2Vbeta8.1); P14 TCRValpha2Vbeta8; P14-TCR; TCR LCMV; TCR P14; TCR-Tg; TgTcr |
| Gene Symbol and Name | Tg(TcrLCMV)327Sdz, transgene insertion 327, Birgit Ledermann |
| Gene Synonym(s) | P14; P14 TCR; P14 TCR-alphabeta (Valpha2Vbeta8.1); P14 TCRValpha2Vbeta8; P14-TCR; TCR LCMV; TCR P14; TCR-Tg; TgTcr |
| Promoter | Tcra, T cell receptor alpha chain, mouse, laboratory |
| Promoter | Tcrb, T cell receptor beta chain, mouse, laboratory |
| Expressed Gene | Tcra, T cell receptor alpha chain, mouse, laboratory |
| Expressed Gene | Tcrb, T cell receptor beta chain, mouse, laboratory |
| Strain of Origin | (C57BL/6 x DBA/2)F2 |
| Chromosome | UN |
| General Note | Transgenic mice carry a T-cell receptor (Tcra-V2, Tcra-J TA31 / Tcrb-V8.1, Tcrb-D, Tcrb-J 2.4) specific for LCMV (lymphocytic choriomeningitis virus), H2-Db. |
| Molecular Note | The transgene carries both Tcra and Tcrb. Ten to twenty copies of the Tcr transgene were reported to have integrated on the same chromosome. At least two transgenic lines are known to exist. Line 327 is the representative line. The second line is 318. |
| Mutations Made By | Dr. Rolf Zinkernagel, University of Zurich |
Disease Terms
Research Areas By Genotype
This mouse can be used to support research in many areas including:
- Research Tools
- Immunology, Inflammation and Autoimmunity Research
- T Cell Receptor Transgenics
- Immunology, Inflammation and Autoimmunity Research
Mammalian Phenotype Terms by Genotype
Genotype: Tg(TcrLCMV)327Sdz/0
involves: C57BL/6 * DBA/2
immune system phenotype
- decreased CD8-positive, alpha-beta T cell number
- number of CD8+ T cells in spleens of transgenic Mlsa mice is reduced 4-fold compared to uninfected transgenic Mlsb but ~4-fold higher than LCMV-infected Mlsb mice (MGI Ref ID J:77696)
- decreased T cell proliferation
- response of uninfected transgenic Mlsa spleen cells to LCMV is reduced ~3-fold (MGI Ref ID J:77696)
- decreased cytotoxic T cell cytolysis
- LCMV-infected Mlsb show decreased significantly reduced proliferation and specific lysis compared to uninfected transgenic mice (MGI Ref ID J:77696)
- lysis of LCMV-infected target cells is decreased ~3-fold in uninfected transgenic mice positive for mixed-lymphocyte stimulatory (Mlsa) antigen compared to transgenic mice positive for Mlsb antigen (MGI Ref ID J:77696)
- decreased double-positive T cell number
- numbers of CD4+CD8+ thymocytes are drastically reduced in LCMV-tolerant (carrier) transgenic mice (MGI Ref ID J:77696)
- thymus hypoplasia
- numbers of double-positive thymocytes and CD8+ thymocytes are drastically reduced in transgenic mice (MGI Ref ID J:77696)
hematopoietic system phenotype
- decreased CD8-positive, alpha-beta T cell number
- number of CD8+ T cells in spleens of transgenic Mlsa mice is reduced 4-fold compared to uninfected transgenic Mlsb but ~4-fold higher than LCMV-infected Mlsb mice (MGI Ref ID J:77696)
- decreased T cell proliferation
- response of uninfected transgenic Mlsa spleen cells to LCMV is reduced ~3-fold (MGI Ref ID J:77696)
- decreased cytotoxic T cell cytolysis
- LCMV-infected Mlsb show decreased significantly reduced proliferation and specific lysis compared to uninfected transgenic mice (MGI Ref ID J:77696)
- lysis of LCMV-infected target cells is decreased ~3-fold in uninfected transgenic mice positive for mixed-lymphocyte stimulatory (Mlsa) antigen compared to transgenic mice positive for Mlsb antigen (MGI Ref ID J:77696)
- decreased double-positive T cell number
- numbers of CD4+CD8+ thymocytes are drastically reduced in LCMV-tolerant (carrier) transgenic mice (MGI Ref ID J:77696)
- thymus hypoplasia
- numbers of double-positive thymocytes and CD8+ thymocytes are drastically reduced in transgenic mice (MGI Ref ID J:77696)
endocrine/exocrine gland phenotype
- thymus hypoplasia
- numbers of double-positive thymocytes and CD8+ thymocytes are drastically reduced in transgenic mice (MGI Ref ID J:77696)
Genotype: Tg(TcrLCMV)327Sdz/?
involves: C57BL/6 * DBA/2J
immune system phenotype
- abnormal T cell differentiation
- T cells expressing the transgene preferentially develop into CD8+ peripheral T cells (MGI Ref ID J:97610)
- there is only minimal rearrangement of endogenous TCRalpha chains needed in double-positive thymocytes to express a transgenic TCR, so that mice have very few CD4 single-positive thymocytes or CD4+ peripheral T cells (MGI Ref ID J:97610)
- decreased CD4-positive, alpha beta T cell number
- very few CD4+T cells are found in the thymus or periphery (MGI Ref ID J:97610)
hematopoietic system phenotype
- abnormal T cell differentiation
- T cells expressing the transgene preferentially develop into CD8+ peripheral T cells (MGI Ref ID J:97610)
- there is only minimal rearrangement of endogenous TCRalpha chains needed in double-positive thymocytes to express a transgenic TCR, so that mice have very few CD4 single-positive thymocytes or CD4+ peripheral T cells (MGI Ref ID J:97610)
- decreased CD4-positive, alpha beta T cell number
- very few CD4+T cells are found in the thymus or periphery (MGI Ref ID J:97610)
References
- Pircher H; Burki K; Lang R; Hengartner H; Zinkernagel RM. 1989. Tolerance induction in double specific T-cell receptor transgenic mice varies with antigen. Nature 342(6249):559-61. PubMed: 2573841MGI: J:77696
Additional References
- Kerry SE; Buslepp J; Cramer LA; Maile R; Hensley LL; Nielsen AI; Kavathas P; Vilen BJ; Collins EJ; Frelinger JA. 2003. Interplay between TCR affinity and necessity of coreceptor ligation: high-affinity peptide-MHC/TCR interaction overcomes lack of CD8 engagement. J Immunol 171(9):4493-503. PubMed: 14568922MGI: J:86195
Additional - Tg(TcrLCMV)327Sdz related
- Agenes F; Dangy JP; Kirberg J. 2008. T cell receptor contact to restricting MHC molecules is a prerequisite for peripheral interclonal T cell competition. J Exp Med 205(12):2735-43. PubMed: 19015305MGI: J:141380
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